Is ASAH1 p.Pro71Ala (c.211C>G) pathogenic?

ASAH1 p.Pro71Ala (c.211C>G) is classified Uncertain significance in ASAH1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-26). AlphaMissense: likely benign (0.0727); Ultra-rare (popmax 0.062%, afr).

How common is ASAH1 p.Pro71Ala (c.211C>G) in the general population?

ASAH1 p.Pro71Ala (c.211C>G) is ultra-rare (popmax 0.062%, afr) (gnomAD).

What do computational predictors say about ASAH1 p.Pro71Ala (c.211C>G)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

ASAH1 p.Pro71Ala

c.211C>G · rs139826635 · VCV284197

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.062%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -2.9, phastCons 1
Regional constraint	o/e 1.37	unconstrained · MANE · 27 kb · p 6.4e-16 · regional, not allelic
Overall
CADD	6.168	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.062% African / African-American · 46/74,152 alleles

Filtering AF 0.0477% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0427%

Overall 0.00299% 47/1,571,510 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.062%	1,612
Remaining individualsnot grpmax-eligible	0.00164%	60,968

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ASAH1
Protein: p.Pro71Ala
Coding: c.211C>G
MANE Select: NM_177924
dbSNP: rs139826635
Type: single nucleotide variant
Location: chr8:18071305 (GRCh38)
Gene constraint: LOEUF 1.435 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.97 · 2 PDB
Residue 71: a disulfide bond; an α-helix

Full ASAH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAH1 p.Pro71Ser Uncertain significance ★ same residue
ASAH1 c.1098+1G>T Pathogenic/Likely pathogenic ★★ same type
ASAH1 c.125+1G>A Pathogenic ★★ same type
ASAH1 c.457+4A>G Pathogenic/Likely pathogenic ★★ same type
ASAH1 c.648+1G>C Likely pathogenic ★★ same type
ASAH1 c.786-2A>G Likely pathogenic ★★ same type
ASAH1 p.Arg254Gly Pathogenic ★★ same type
ASAH1 p.Arg296Ter Pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/asah1-p-pro71ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown